Mechanisms of the McMurry Reaction

As noted above, there was apparently no doubt about the involvement of pinacolate intermediates in the McMurry reaction and the main questions concerned instead the nature of the active spedes, and in particular its oxidation state. 

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The synthetic method leading to Nb-alkylidenes and Nb-alkylidynes was particularly successful, due to a quite remarkable difference in the reaction rate of 29 with ketones or aldehydes, vs the subsequent reaction of the alkylidene with ketones and aldehydes (see Scheme 37). The former reaction takes a few minutes at -40°C, while the latter one occurs in hours at room temperature.88 The reaction between 178 and benzaldehyde led to triphenylethylene and the niobyl derivative 184. Due to the difference in reaction rates between a and b in Scheme 37, it was found that the sequential addition of two different ketones or aldehydes to a THF solution of 29 produced a nonsymmetric olefin in a stepwise McMurry-type reaction.84 This is exemplified in the coupling shown in reaction c (Scheme 37). The proposed reaction pathway does not involve the intermediacy of a pinacolato ligand and therefore differs from the mechanism of the McMurry reaction and related reductive couplings at activated metal sites.89... 

For many years the elucidation of the mechanism of the McMurry reaction has been complicated by the fact that the most commonly used low-valent titanium was derived from hour-long pre-reducing DME-complexed TiCl3 with a zinc/copper couple (DME is 1,2-dimethoxyethane). Apparently, however, the zinc/copper couple reacts with TiCl3 only if the carbonyl compound is present, too. This fact has become part of the current mechanistic view of the McMurry reaction (Figure 17.58). At the same time, it became the starting point of the following variants of the McMurry reaction ... 

Fig. 17.58. The mechanism of the McMurry reaction. A mixture of diastereomers of the dititanium(III) glycolate C is either directly generated via the initially formed Ti(in) ketyl B (variant 1) or in multiple steps (variant 2). At sufficiently high temperatures, C is then reduced to a mixture of diastereomers of the corresponding dititanium(III) glycolate G. The latter decomposes via homolytic cleavage of one of its C—0 bonds to furnish the radical intermediate H. If the only C—0 bond left in this radical also breaks homolytically—which partly occurs without ( ) prior rotation around the C-C(OTiCl) bond—the alkene is formed as an F,Z-mixture. Its composition may (somewhat) depend on the configuration of the dititanium(II) glycolate precursor G (cf. Figure 17.56).

Fig. 14.49. Mechanism of the McMurry reaction. The heterocyclic monotitanium glycolates A and B or analogous dititanium glycolates decompose at higher temperatures via heterolytic cleavage of one of their C—O bonds and form the radical intermediate C. The alkene is formed by cleavage of the second C—O bond. This alkene is not obtained as a single stereoisomer because of the free rotation about the C—C(O) bond in the radical intermediate C. Note that the alkene is formed with a cis, fraraj-selectivity that is independent of the configuration of the titanium glycolate precursor(s).

Stahl M, Pidun U, Erenking G (1997) On the mechanism of the McMurry reaction. Angew Chem Int Ed Engl 36 2234... 

Villiers, C., Ephritikhine, M. New insights into the mechanism of the McMurry reaction. Angew. Chem., tnt. Ed. Engl. 1997, 36, 2380-2382. 

Scheme 6.1. The two mechanisms of the McMurry reaction proposed by Mukaiyama et al. (top) and by Tyrlik and Wolochowicz (bottom).

Such considerable improvements were possible after the design of more reactive low-valent titanium species and the use of new synthetic methods and procedures these will be presented in the second part of this chapter. In comparison with its synthetic applications, the mechanism of the McMurry reaction has received much less attention, undoubtedly because chemists were firmly convinced of the involvement of pinacolate intermediates and rejected, in spite of some evidence, the alternative pathway via carbenoid species. The last part of this chapter will describe the recent studies on the structure and mode of action of low-valent titanium species, as well as some accurate analyses of the reaction products, which have allowed new insights into the mechanism, revealing its dual nature. 

McMurry coupling reaction. The mechanism of the McMurry coupling reaction consists of two defined steps the reductive dimerization of the... 

The mechanism of the McMurry coupling is not entirely clear, but it is composed of two distinct steps 1) pinacol formation and 2) deox genation to the alkene. Extensive research showed that the low-valent titanium is most likely a mixture of Ti " and Ti ° , and the ratio of these species depends on the method of preparation (solvent, temperature, reducing agent, J ecent findings suggest that the reaction possibly involves the formation of a carbene or a metal carbenoid. The nature of the intermediates is strongly dependent on the structure of the carbonyl substrate and the reaction conditions, which is why the reaction is tricky and yields are difficult to reproduce in the laboratory. 

Figure 13.7. Mechanism of the McMurry coupling reaction. [Reprinted with permission from McMurry, J.E. Fleming, M.P. Kees, K.L. Krepski, L.R. J. Org. Chem., 1978, 43, 3255. Copyright 1978 American Chemical Society.]...

The McMurry reaction does not cease to find new important applications, despite some pervasive problems of reproducibility new practical reagents and simplified methods have been developed, but rather complicated systems are still necessary for obtaining higher selectivities. These contradictory features of the McMurry reaction, which leave many challenges for further study, and the dual nature of its mechanism, reinforce the fascinating character of this versatile transformation, which is irreplaceable in organic synthesis. 

The proposed catalytic mechanism for intramolecular McMurry reaction begins with the reduction of TiCl3 by zinc metal to generate the activated titanium species A-19. Reductive cyclization of the dicarbonyl substrate forms the McMurry coupling product, along with titanium oxide complex B-15. To close the catalytic cycle, the oxide complex B-15 is converted to TiCl3 by Me3SiCl (Scheme 63).8d,8e... 

We expect you to be mildly horrified by the inadequacy of the mechanism above. But, unfortunately, we can t do much better because no-one really knows quite what is happening. The McMurry reaction is very useful for making tetrasubstituted double bonds—there are few other really effective ways of doing this. However, the double bonds really need to be symmetrical (in other words, have the same substituents at each end) because McMurry reactions between two different ketones are rarely successful. 

ACTIVE FIGURE 7.6 MECHANISM Mechanism of the acid-catalyzed electrophilic addition of HjOto 2-methyl-propene to give the alcohol 2-methylpropan-2-ol. The reaction involves a carbocation intermediate. Co to this book s student companion site at www.cengage.com/chemistry/ mcmurry to explore an interactive version of this figure. 

This process is similar to the Mcmurry reaction [167] the reductive dimerization of aldehydes and ketones by [Ti] forming oleftnic C=C bonds. The mechanism of the Furstner synthesis presumably involves single-electron transfer to the carbonyl groups (78 -> 80) and intramolecular radical combination in 80 (supported by Ti-chelation) to... 

The mechanisms of these reactions bear marked similarities, in spite of the differences in their reactivities and selectivities. Thus, in certain cases, a four-membered intermediate similar to the 1,2-oxaphosphetane intermediate in the Wittig reaction appears in the Peterson reaction as a pentacoordinate 1,2-oxasiletanide. Reactions of transition metal carbene complexes with carbonyl compounds also proceed through the formation of a four-membered oxametallacycle, which was recently found to be an intermediate of some McMurry reactions. Carbonyl olefination utilizing dimetallic species of zinc or chromium is somewhat similar to the Julia reaction in that they both involve the process of ) -elimination. 

The reaction is a versatile strategy for carbon-carbon bond construction as evidenced by the large number of natural and non-natural compounds that have been synthesized using the McMurry reaction as a key step. Furthermore, the reaction has stimulated a significant number of theoretical studies, including examinations of the unique and often highly-strained molecules that can be prepared using the McMurry reaction and of the mechanism of the reaction itself. 

Measurements of the urban aerosol mass distribution have shown that two distinct modes often exist in the 0.1 to 1.0 pm diameter range (Hering and Friedlander 1982 McMurry and Wilson 1983 Wall et al. 1988 John et al. 1990). These are referred to as the condensation mode (approximate aerodynamic diameter 0.2 pm) and the droplet mode (aerodynamic diameter around 0.7 pm). These two submicrometer mass distribution modes have also been observed in nonurban continental locations (McMurry and Wilson 1983 Hobbs et al. 1985 Radke et al. 1989). Hering and Friedlander (1982) and John et al. (1990) proposed that the larger mode could be the result of aqueous-phase chemical reactions. Meng and Seinfeld (1994) showed that growth of condensation mode particles by accretion of water vapor or by gas-phase or aerosol-phase sulfate production cannot explain existence of the droplet mode. Activation of condensation mode particles, formation of cloud/fog drops, followed by aqueous-phase chemistry, and droplet evaporation were shown to be a plausible mechanism for formation of the aerosol droplet mode. 

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